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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 433 records · Page 24Linked to original sources
PubMed1992

[Inhibition of serotonin-induced platelet aggregation by endothelins].

Endothelins are a family of three peptides that act as local hormones in all mammalian species. They were found to inhibit rabbit and dog platelet aggregation in vivo, whereas no effect was observed in vitro. In order to investigate the possible interaction between endothelins and human platelet serotonergic receptors, their effect on the platelet aggregation, induced by serotonin, was studied. Endothelin-1, -2 and -3 had a dual action for platelet aggregation induced by serotonin. When added simultaneously to serotonin endothelins aggregatory response to this amine was potentiated. On the contrary, preincubation of platelet suspension with endothelins resulted in a concentration-dependent inhibition of serotonin-promoted platelet response. Moreover, endothelin-1 inhibited serotonergic amplification of epinephrine-induced aggregation of platelets. It is proposed that endothelins bind to the platelet membrane and interact with serotonergic receptors and/or G proteins. The diverse effect of eodothelins on serotonin-induced aggregation of platelets may be due to stimulation of protein kinase C.

Blood Platelets↗
PubMed1992

Effects of probucol on low-density lipoprotein catabolism in guinea pigs.

We studied the effects of administering probucol on the catabolism of low density lipoprotein (LDL) in guinea pigs. Probucol administration significantly lowered the levels of total and LDL-cholesterol in animals given either normal chow or the high cholesterol (1% W/W) diet. High-density lipoprotein cholesterol was decreased significantly in the animals fed cholesterol, but not normal chow diet. Triglyceride levels were unaffected in both groups. No significant changes were observed in the LDL receptor-dependent and LDL receptor-independent catabolism of native LDL and LDL obtained from a probucol-treated patient. However, when the LDL isolated from a probucol-treated patient was injected, the fractional catabolic rate was significantly lower than that of injected native LDL. This study indicates that probucol lowered the plasma LDL cholesterol level neither by an increased catabolism of LDL via an LDL receptor nor an LDL receptor-independent pathway.

Animals↗
PubMed1991

[Effect of growth hormone on immune function in normal and hypophysectomised rats].

The effect of growth hormone (GH) on immune function was studied using normal and hypophysectomised male Wistar rats. Hypophysectomy was performed by the auditory approach at 4 weeks of age. Normal and hypophysectomised rats were treated with saline or 0.4IU/body GH daily during 7 to 11 weeks of age. Histological features of the thymus and spleen and immunological parameters including blood cell counts, lymphocyte subsets, serum immunoglobulin levels, splenic natural killer activity, and mitogen-induced splenic lymphocyte proliferation were examined in the rats at 11 weeks of age. In hypophysectomised rats, the counts of peripheral white blood cells (5,513 +/- 813/microliters), lymphocytes (4,838 +/- 737/microliters), Th/i cells (2,237 +/- 329/microliters), and B cells (1,400 +/- 509/microliters), Th/i/Ts/c ratio (1.78 +/- 0.27), splenic T cell subsets (pan T: 51.0 +/- 4.3%, Th/i: 31.6 +/- 3.0%, Ts/c: 23.9 +/- 2.7%), and serum IgG level (2,148 +/- 470mg/l) were significantly decreased as compared with normal rats. Natural killer activity (17.8 +/- 4.6%) and mitogen-induced proliferation of T cells (Con A: 47.1 +/- 15.7, PHA: 51.6 +/- 12.5) were also suppressed. Hypoplasia of the thymus and spleen was observed in parallel to retarded growth of the rats. In contrast, GH supplement to the hypophysectomised rats resulted in increases in growth and lymphoid tissue, and the restoration of the counts of peripheral white blood cells (6,850 +/- 840/microliters), lymphocytes (6,211 +/- 731/microliters), Th/i cells (2,909 +/- 304/microliters), and B cells (1,947 +/- 402/microliters), Th/i/Ts/c ratio (2.04 +/- 0.34), serum IgG level (3,414 +/- 1,326mg/l), and natural killer activity (25.7 +/- 4.7%). However, splenic lymphocyte subsets and mitogen-induced proliferation of T cells were not recovered by GH treatment for 4 weeks. GH administered to normal rats increased serum IgG level (4,982 +/- 1,496mg/l) but did not affect other immunological parameters. These results indicate that humoral and cell-mediated immune function are impaired in hypophysectomised rats, but GH supplement administered to them restored most of the impaired immune function, suggesting that GH plays an important role in the development of immune function.

Animals↗
PubMed1991

Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers.

Diurnal changes of serotonin-related factors in whole blood and fibrinolytic activity were determined in depressed patients and healthy controls. Whole blood serotonin concentration of depressed patients showed marked changes throughout daytime, with maximum values in the evening and lowest values in the morning, whereas its metabolite 5-HIAA followed a contrary pattern. The circadian rhythm of 5-HT and 5-HIAA in the control group was quite different from depressed patients. Plasma levels of tPA decreased from 12:30 to 16:30. Concentrations of free plasminogen activator inhibitor (PAI-1) and complex of tPA-PAI-1 decreased from 8:30 to 16:30. Plasma levels of total PAI-1 decreased from 8:30 to 16:30. Plasma levels of the fibrinolytic parameters may be lower in depressive patients than in normal controls. These results support the changes in the circadian rhythm of serotonin and its related substances in the blood of depressive patients.

Adult↗
PubMed1991

PAI-1 plays an important role in the expression of t-PA activity in the euglobulin clot lysis by controlling the concentration of free t-PA.

The antigen levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were assayed in the plasma and in the euglobulin fraction, and their contributions to the euglobulin clot lysis time (ECLT) and t-PA activity were analyzed. Total and free PAI-1 levels in both fractions showed significant positive correlation with ECLT (p less than 0.001), whereas t-PA antigen level did not have a high correlation coefficient with ECLT. t-PA activity showed significant negative correlation with ECLT (p less than 0.001) and positive correlation with free t-PA level (p less than 0.001), which was calculated by the ratio of the concentrations of t-PA-PAI-1 complex and the free PAI-1. Thus free t-PA seems to dissolve the euglobulin clot and its concentration seems to be controlled by the concentration of free PAI-1. These findings were confirmed by the analyses of the effects of C1-inactivator and antibody against t-PA to regular ECLT and kaolin activated ECLT, the latter of which was only inhibited by the addition of C1-inactivator whereas the former was inhibited by anti-t-PA antibody.

Adolescent↗
PubMed1991

[SPECT images after intravenous injection of 99mTc-DTPA in lung tumors--comparison with delayed 123I-IMP lung scintigraphy].

The aim of this study was to assess the efficacy of SPECT imaging of the thorax with 99mTc-DTPA, which accumulates at sites of increased capillary permeability and expanded extracellular space, by comparing it with delayed 123I-IMP lung scintigraphy. We have previously reported that increased uptake on delayed 123I-IMP lung scintigraphy was associated with atelectasis and inflammation. Thirteen patients with lung cancer (4 with atelectasis and 3 with pleurisy), one patient with malignant lymphoma complicated by pneumonia and pleurisy, and one patient with pneumonia were studied. 99mTc-DTPA scintigraphy was performed twice, 20-160 minutes and 2-4 hours after the intravenous administration of 370 MBq of 99mTc-DTPA. 123I-IMP scintigraphy was performed 24 hours after the intravenous injection of 111 MBq of 123I-IMP. SPECT images were obtained with both types of scintigraphy. 99mTc-DTPA scintigraphy was compared with 123I-IMP scintigraphy for its ability to detect atelectasis and pneumonia. All patients showed increased accumulation corresponding to the lesions on both 123I-IMP and 99mTc-DTPA scintigraphy. 123I-IMP scintigraphy showed a defect corresponding to the tumor with increased accumulation around the tumor, whereas 99mTc-DTPA scintigraphy showed accumulation corresponding to the tumor. Ten of 11 tumors showed accumulation of an intensity equal to that of the soft tissue of the chest wall on 20-60 min 99mTc-DTPA images. The 2-4 hr images showed that 99mTc-DTPA leaked from the periphery of the tumor toward its center. All the patients with pleurisy showed increased accumulation in effusion on 2-4 hr 99mTc-DTPA scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Carbachol enhances forskolin-stimulated cyclic AMP accumulation via activation of calmodulin system in human neuroblastoma SH-SY5Y cells.

We have investigated the modulatory action of carbachol on intracellular cAMP levels in human neuroblastoma SH-SY5Y cells. Carbachol enhanced forskolin-stimulated cAMP levels in a dose-dependent manner (EC50 = 3 microM). The enhancing effect of carbachol was completely inhibited by pirenzepine and atropine. Pertussis toxin treatment of the cells partially affected the ability of carbachol. Furthermore, carbachol also enhanced the effect of vasoactive intestinal peptide (EC50 = 3 microM)-, adenosine- and prostaglandin E1-stimulated cAMP levels. The enhancing response of carbachol was sensitive to trifluoperazine but insensitive to calphostin C. These results suggest that the mechanism for carbachol-induced cAMP levels may act, at least in part, through the activation of calmodulin system in SH-SY5Y cells. Hence we describe for the first time a synergistic interaction between calmodulin- and cAMP-dependent signal transduction pathway mediated by carbachol in neuron-derived cell line.

Adenosine↗
PubMed1991

Increase in levels of plasminogen activator and type-1 plasminogen activator inhibitor in human breast cancer: possible roles in tumor progression and metastasis.

We measured antigen levels of two kinds of plasminogen activators, tissue type plasminogen activator (t-PA) and urokinase type plasminogen activator (UK), as well as their primary inhibitor, type-1 plasminogen activator inhibitor (PAI-1) in the tissue extracts of benign and malignant breast tumors. Tumor tissues of 36 fibroadenomas and 39 breast cancers were examined. t-PA levels were not different in both groups. Malignant tumors contained the significantly higher levels of UK than benign tumors (p less than 0.001). Furthermore in breast cancer tissues, UK antigen levels of tumors with axillary lymph node involvements were significantly higher than those of tumors without lymph node involvements (p less than 0.05). PAI-1 antigen levels of breast cancer tissues were dramatically higher than those of fibroadenoma (p less than 0.001). PAI-1 levels of node positive carcinomas showed also values significantly higher than node negative ones (p less than 0.01). When we divided cancer tissues into three groups as node negative tumors, tumors with positive axillary nodes fewer than four and tumors with four or more positive nodes, PAI-1 levels increased corresponding to the progression of lymph node involvements (p less than 0.05). Immunohistochemical studies, using mouse monoclonal antibodies to human UK and PAI-1, showed that those immunoreactivities were diffusely distributed in the cytoplasm of human breast cancer cells. Their staining patterns were very similar to each other.

Adenofibroma↗
PubMed1991

The activation of plasminogen by T-PA-PAI-1 complex in the absence of fibrin.

The activity of tissue plasminogen activator-plasminogen activator inhibitor-1 (t-PA-PAI-1) complex to convert plasminogen to plasmin was examined by using fibrin autography and casein zymography where plasminogen was added or removed for casein layer. Fibrin autography was more sensitive to the activity of t-PA even in the complex with PAI-1, but casein zymography was more sensitive to plasmin. The inhibitory activity of PAI-1 toward t-PA diminished when plasma was clotted, thus in the presence of fibrin. These results indicate that t-PA-PAI-1 complex has a catalytic activity even in the absence of fibrin, but the activity is enhanced in its presence.

Fibrin↗
PubMed1991

The effects of polysaccharides on plasminogen activation by single chain-and two chain-tissue plasminogen activator.

We examined the effects of polysaccharides on t-PA mediated plasminogen activation using single-chain tissue plasminogen activator (sct-PA) and two-chain tissue plasminogen activator (tct-PA). Unfractionated heparin, low molecular weight heparin (LMW heparin) and dextran sulfates enhanced the activation rate of plasminogen by sct-PA about three-fold to six-fold. Chondroitin sulfate C did not enhance the activation. The activation of plasminogen by tct-PA was slightly enhanced by unfractionated heparin, but not by other polysaccharides. Conversion of sct-PA to tct-PA was not stimulated by polysaccharides. SDS-PAGE showed no enhancement of the conversion from sct-PA to tct-PA by plasmin in the presence of polysaccharides. However, the enhancement of sct-PA mediated activation of plasminogen by unfractionated heparin, LMW heparin and dextran sulfates in the presence of aprotinin was shown with SDS-PAGE. It was suggested that unfractionated heparin, LMW heparin and dextran sulfates form complex with sct-PA and plasminogen, and stimulate the conversion of sct-PA to tct-PA.

Animals↗
PubMed1991

Stimulation of the amidolytic activity of single chain tissue-type plasminogen activator by fibrinogen degradation products: possible fibrin binding sites on single chain tissue-type plasminogen activator molecule.

The steady-state kinetics of the amidolytic activity of single chain tissue-type plasminogen activator (tPA) were analyzed in the presence or absence of different molecular forms of fibrinogen degradation products. Single chain tPA showed a Km value of 1.6 mM and kcat value of 4.9/s toward the chromogenic substrate H-D-Ile-Pro-Arg-p-nitroanilide (S-2288). In the presence of infinite concentrations of fibrinogen, kinetic constant was calculated as about 8-times higher than that in the absence of fibrinogen, mainly caused by the decrease of Km value. The dissociation constant (Ka) for this stimulation by fibrinogen was 2.9 microM. When the same assay was conducted with fragment X or fragment D of fibrinogen, the kinetic constants increased 3.2 and 2.9-times, respectively, whereas no enhancement was obtained by fragment E. Neither lysine analogues nor monoclonal antibody toward domains of finger and epidermal growth factor of tPA quench the enhancement by fibrinogen. This enhancement was not observed in the case of the two chain form of tPA. These results indicate that fibrinogen enhances the amidolytic activity of single chain tPA by binding to kringle 2 domain or light chain through D domain of fibrinogen.

Binding Sites↗
PubMed1991

In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells.

Cloned integrin alpha 2 subunit complementary DNA was expressed on human rhabdomyosarcoma (RD) cells to give a functional VLA-2 (alpha 2 beta 1) adhesion receptor. The VLA-2-positive RDA2 cells not only showed increased adhesion to collagen and laminin in vitro, but also formed substantially more metastatic tumor colonies in nude mice after either intravenous or subcutaneous injection. These results show that a specific adhesion receptor (VLA-2) can markedly enhance both experimental and spontaneous metastasis. In contrast to the metastasis results, there was no difference in either the in vitro growth rate or apparent in vivo tumorigenicity of RD and RDA2 cells.

Animals↗
PubMed1991

Radioimmunoassay for activin A/EDF. Method and measurement of immunoreactive activin A/EDF levels in various biological materials.

A radioimmunoassay (RIA) for the measurement of activin A, which is identical to erythroid differentiation factor (EDF), has been developed. A specific antiserum against activin A/EDF was raised in rabbits using a mixture of recombinant EDF and polyvinyl pyrrolidone. Of the compounds tested this polyclonal antibody cross-reacted only with bovine inhibin (3.2%) and human TGF-beta (4.2%). The least detectable value in this assay was 0.06 ng/tube. The within- and between-assay coefficients of variation at three different concentrations were 3.6-9.8% and 3.4-7.7%, respectively. Using this RIA, immunoreactive activin A/EDF levels in various biological fluids and tissues were examined. The dose-response curves of porcine follicular fluid and ovarian extract were parallel to the standard curve, and porcine follicular fluid contained high activin A/EDF immunoreactivity (1050 ng/ml). On gel chromatography of porcine follicular fluid, the major immunoreactivity was eluted in the same position as authentic activin A/EDF. Human placental extract and amniotic fluid had relatively high immunoreactive activin A/EDF levels (174 ng/g wet wt. and 63.9 ng/ml, respectively), but the dose-response curve of amniotic fluid was not parallel to the standard curve. Among rat tissues, the ovary showed the highest activin A/EDF immunoreactivity (163 ng/g wet wt.) much lower than that of porcine ovary (1020 ng/g wet wt.). Low immunoreactive activin A/EDF levels were detected in most parts of rat brain (8.7-14.2 ng/g wet wt.), except for the pituitary gland (70.0 ng/g wet wt.). The initial plasma half clearance time (t1/2) of exogenous activin A/EDF was 14 min in the rat and the plasma FSH concentration did not change significantly during this period. These results suggest that this RIA system has sufficient sensitivity and specificity to measure activin A/EDF concentrations in biological materials, and that the reproductive tissues are the main sources of activin A/EDF.

Activins↗